We propose to develop a biological model to be used for the demonstration and quantitation in vivo of hematopoietic toxicity produced by pollutants, therapeutic compounds, and other chemicals. The great hematopoietic reserve in normal mice will first be eliminated by a combination of splenectomy and the production of standardized damage of the hematopoietic system with 89Sr, a bone-seeking, beta-emitting isotope. In this model, which we presume will be more sensitive to hematopoietic toxins than normal animals, the fall in hematrcrit, reticulocyte count, white cell count, platelet count, and marrow concentration of colony-forming units (stem cells) will then be determined and the hematopoietic response to a standardized challenge with erythropoietin or hypoxia will then be measured as functions of the dosage of hematopoietic toxins administered. The duration of the persistence of defects produced by toxic substances will also be determined. The thesis that residual hematopoietic damage is, at least in part, a function of stromal damage will be investigated. Regeneration of hematopoietic functional capacity and reserve will be sought by implantation of syngeneic marrow cells or hematopoietic stroma. Finally, the chemicals identified in this study to exert hematopoietic toxic effects will be studied for leukemogenic or co-leukemogenic (with irradiation) potential in the RF mouse.